B-cell chronic lymphocytic leukemia (CLL), the most common leukemia in North America, is a disease of CD5+ B lymphocytes characterized by slow proliferation and decreased apoptosis. The decreased apoptotic death of CD5+ B lymphocytes contributes to their increased abundance in blood, producing the clinical entity of CLL.
The progression of this disorder is often indolent, with a median survival over 20 years from the time of diagnosis (Chiorazzi et al. (2005) N Engl J Med 352, 804-15; Keating, M. J. (2002) in Leukemia, eds. Henderson et al. (Saunders, Philadelphia), pp. 131-151). CLL is characterized by overexpression of anti-apoptotic proteins such as bcl-2, and commonly employed therapies in CLL increase apoptotic cell death. Activation of the PI-3-K/Akt pathway in CLL cells can inhibit apoptotic death (Cuni et al. (2004) Leukemia 18, 1391-400).
Many therapies for CLL cause leukemia cell death by triggering apoptosis. However, there is need for more effective prognosis and treatment options for diseases such as CLL.